Coeliacs yearn for genetics to win the battle
Research into coeliac disease offers the hope that non-dietary treatments could be tailored to a person’s genes, writes Lynnette Hoffman
EVER since she was diagnosed with coeliac disease a year ago, Sophie Stone has diligently stuck to the gluten-free diet required to keep symptoms at bay. She checks food labels religiously, interrogates waiting staff at restaurants as soon as she arrives, and explains her situation to anyone who invites her in for a meal. But awkward situations still arise.
A recent dinner comes to mind. The hosts had taken great care to ensure that gluten — a sticky protein found in wheat, rye, barley and oats — wasn’t on the menu. They’d prepared all sorts of meat to barbecue and even made a gluten-free pasta salad. But they’d forgotten to check ingredients in the marinade — and many typical marinade staples, such as soy sauce and oyster sauce, contain gluten. This one was no exception.
Not wanting to insult them, Stone ate the meat — and spent much of the night in the bathroom feeling its effects.
Ironically, before she stopped eating gluten, Stone suffered few of the gastro-intestinal symptoms that characterise the disease. But now she’s hypersensitive, and even trace amounts make her sick.
In coeliac disease, which can develop at any age, gluten triggers an immune response that damages the small intestine. The villi, the finger-like projections that line the small intestine and absorb the nutrients you eat, become flatter, shorter, and in some cases are lost completely. It’s that visible physical damage that distinguishes coeliac disease from the more common gluten intolerance, where a person experiences severe gastrointestinal problems from gluten.
When the villi become damaged the ability to absorb nutrients is dramatically reduced, leaving people prone to iron deficiency, fatigue, low bone density, osteoporosis and infertility. It can be especially dangerous in undiagnosed pregnant women, whose fetuses might not be getting the vitamins and minerals they need, putting them at double the risk of adverse outcomes and birth defects such as spina bifida.
Currently the only available treatment is a life-long gluten-free diet, and while it works to prevent intestinal damage and malnutrition, it is no cure and leaves patients vulnerable if they consume gluten by mistake. And a gluten-free diet isn’t easy.
Stone can testify to that. Gluten-free diets are gaining popularity so suitable products are increasingly available, but they are signifi- cantly more expensive. Take gluten-free bread, for example. ‘‘ It’s out there, but nine times out of 10 you’ll pay something like $7 for a loaf that’s half the size (of normal bread),’’ Stone says. Pasta is about four times the price.
It’s not just about price. Gluten is one of the components of wheat flour that helps to make dough stick together, so bread, pasta and other products made without it have an unfamiliar — many would say unpleasant — texture.
Many gluten-free breads are crumbly, like stale cake without the sugar. As for the pasta, you have to watch it closely or it falls apart, she says. And the taste? Stone says she has finally found a gluten-free bread she can endure, but in general it’s much heavier and more dense. But the real frustration is the hassle. ‘‘ It limits my whole lifestyle. You don’t have as much freedom to be spontaneous,’’ she says. Even foods that are in theory gluten-free, such as hot chips, may not be, if, for example, the oil they’ve been cooked in has been tainted with other products such as battered fish.
In a person with coeliac disease, consuming just 50mg of gluten — about the same as 1/100th of a slice of bread — is enough to damage the small intestine.
If there was an alternative treatment available, Stone says she’d be among the first to put her hand up for it.
Now Victorian research published in the current issue of the journal Immunity has shed new light into the way the disease works at a molecular level, bringing closer the possibility of new non-dietary treatments ( Immunity 2007;27:1-12).
The study shows that a person’s immune response differs depending on the particular genes they have — meaning that to be effective, treatments would need to be tailored for the different gene combinations most commonly found in people with the disease.
There’s a strong genetic link in coeliac disease. Almost all patients (99.6 per cent) have either a gene known as DQ2, a gene called DQ8, or both — although they alone don’t cause the disease. Thirty to 40 per cent of the population has either one of those genes, but only 1 per cent has coeliac disease, meaning environmental factors also play a role. Some people — such as those whose family members have already been diagnosed with the disease, as well as people with type 1 diabetes or thyroid disease, are also at a higher risk of coeliac disease.
Until now nearly all research into nondietary treatments of coeliac disease focused on the 80 per cent of people who have only the DQ2 gene. Researchers had already figured out the process that made gluten toxic in people with DQ2-associated coeliac disease and assumed it would be much the same for the minority of people with the DQ8 version.
They assumed any potential treatment could apply to either. But it turns out that’s not the case, says doctor Bob Anderson, a gastroenterologist at the Walter and Eliza Hall Institute, and an author of the latest study.
‘‘ This is the first time we’ve begun to look beyond the core 80 to 90 per cent of people with coeliac disease who have the DQ2 gene — the DQ8 have been slightly overlooked,’’ Anderson says. ‘‘ At the molecular level there’s quite a different immune response to the gluten.’’
For example, in people with DQ2-associated coeliac disease, parts of the protein that trigger an immune response aren’t being properly digested. Because people with coeliac disease are hyper-sensitive to gluten, their T cells recognise the undigested bits as invading pathogens, and respond aggressively. Some scientists are looking at how enzymes could break down the protein better and reduce the immune response.
‘‘ In people with DQ8, the relevant parts of the gluten are already efficiently digested, so using an enzyme wouldn’t necessarily be beneficial,’’ Anderson says.
So one of the possible treatments researchers are looking at is a desensitisation vaccine that would use the parts of the protein that are specifically relevant to DQ8 to shut down the T-cell so it becomes tolerant of the gluten. Scientists at the Walter and Eliza Hall Institute are currently working on another version of the vaccine aimed at the DQ2 gene.
In the last four years doctors have been using a gene test to rule out coeliac disease — but to actually make a diagnosis they need a biopsy of the bowel to look for signs of damage. Ultimately researchers hope the gene test will help doctors decide what treatment the patient would benefit most from.
But any non-dietary treatment is still at least a few years away, Anderson says, so for now the gluten-free diet is it.
When coeliac patients manage to completely avoid gluten, their intestine does heal. So if you suspect you may have coeliac disease, experts say you should not cut out gluten unless you’ve actually had a biopsy to make the diagnosis. If you do it the other way around you may get a false negative, says Sue Shepherd a dietitian in the department of gastroenterology at Box Hill Hospital, who specialises in ceoliac disease.
‘‘ It varies, but it can take up to two years for the small bowel lining to fully heal,’’ Shepherd says, while the gastrointestinal symptoms can disappear much more quickly.
‘‘ For some people they are gone after the first few days of a gluten-free diet and for others it takes months. Symptoms of fatigue can also improve in a matter of weeks for some people, or months for others.’’
Common symptoms of coeliac disease include bloating, wind, pain, diarrhoea or constipation or both, fatigue and iron deficiency.
‘‘ People can eat gluten without feeling unwell, but still be causing damage on the inside,’’’ Shepherd says.
In fact, she says, there is no link between the severity of symptoms and the amount of damage to your small intestine. Research she did as part of her PhD that looked at 101 coeliac patients found 30 per cent had no symptoms — but 82 per cent of that group had serious damage to their intestine.
No matter how mild or silent the symptoms, everyone diagnosed with coeliac disease ‘‘ requires the same strict life-long gluten free diet’’, Shepherd says. At least for now.
Compromised: Sophie Stone says coeliac disease almost prohibits spontaneity in her life